41 research outputs found

    Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage

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    The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has previously been shown to cause a human progeroid disorder, Néstor–Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly [ADP-ribose] polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions

    Processing of protein ADP-ribosylation by Nudix hydrolases

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    ADP-ribosylation is a post-translational modification (PTM) of proteins found in organisms from all kingdoms of life which regulates many important biological functions including DNA repair, chromatin structure, unfolded protein response and apoptosis. Several cellular enzymes, such as macrodomain containing proteins PARG [poly(ADP-ribose) glycohydrolase] and TARG1 [terminal ADP-ribose (ADPr) protein glycohydrolase], reverse protein ADP-ribosylation. In the present study, we show that human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro, converting it into ribose-5'-phosphate (R5P) tags covalently attached to the modified proteins. Furthermore, our data show that hNUDT16 enzymatic activity can be used to trim ADP-ribosylation on proteins in order to facilitate analysis of ADP-ribosylation sites on proteins by MS

    A Review on Possible Approaches for Detecting Early Warning Signs in Projects

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    In this paper, we attempt to provide an overview of the full extent of early warning detection approaches, which are directly or indirectly addressed in the literature. These approaches can aid project managers in taking corrective actions timely enough for preventing failures. The study is based on a review of the current literature within the field of early warning in project management and our own experiences gained from practice. An analysis of the strengths and weaknesses of each approach and their applications in different contexts are also performed. We conclude that the choice of the most effective approach is arguably dependent on the type of project, organizational culture, and the project environment

    Fatores críticos de sucesso à adoção de GSCM: estudo de casos no setor de baterias automotivas

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    This study aimed to analyze how the major manufacturers of automotive batteries in Brazil, considered as focal companies in their supply chains, perceive the influence of critical success factors (CSFs) for adoption of green supply chain management (GSCM) practices. A case study was carried out in the three leading manufacturing companies in this sector using data source triangulation: interviews with company managers, coordinators, and supervisors; on site observations of operational activities; and secondary data. The relationship between CSF variables and GSCM practices was investigated. The main results obtained include: “top management commitment” is the most critical success factor for the effective adoption of GSCM practices and that “information management” and “training” (indirectly) are highly critical for adoption of a number of GSCM practices. This study provides deeper insights into this fairly recent topic
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